The principal goals of the proposed research are to obtain a detailed understanding of the processes which initiate sickle hemoglobin aggregation and of the interactions which stabilize the resulting aggregate structure. We also plan to characterize the effects of several small molecules which appear to affect the aggregation process. This work will utilize both conventional and several recently developed magnetic resonance techniques to permit detailed studies at a molecular level. The expected significance of this work will be in developing a further understanding of the sickle hemoglobin aggregaton process, and in developing information necessary for the systematic design of aggregation inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL023697-06
Application #
3337368
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1979-09-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Pharmacy
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Prabhakaran, M; Johnson, M E (1993) Molecular dynamics of sickle and normal hemoglobins. Biopolymers 33:735-42
Manavalan, P; Prabhakaran, M; Johnson, M E (1992) Location of potential binding sites on deoxy hemoglobin for the design of antigelling agents. J Mol Biol 223:791-800
Xu, Y; Prabhakaran, M; Johnson, M E et al. (1990) Secondary structure prediction for the spectrin 106-amino acid segment, and a proposed model for tertiary structure. J Biomol Struct Dyn 8:55-62
De Croos, P Z; Sangdee, P; Stockwell, B L et al. (1990) Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia. J Med Chem 33:3138-42
Yuan, C J; Hopfinger, A J; Johnson, M E (1989) QSAR and molecular shape analysis of aryl-substituted alanine analogs as antigelling agents. J Theor Biol 141:41-52
Fung, L W; Lu, H Z; Hjelm Jr, R P et al. (1989) Quantitative detection of rapid motions in spectrin by NMR. Life Sci 44:735-40
Thiyagarajan, P; Johnson, M E (1987) Saturation-transfer electron paramagnetic resonance detection of anisotropic motion by sickle hemoglobin molecules in the polymer state. Biochemistry 26:1903-9
Hjelm Jr, R P; Thiyagarajan, P; Johnson, M E (1986) CD of gels and suspensions: apparent CD in the soret region of sickle hemoglobin gels. Biopolymers 25:1359-78
Fung, L W; Lu, H Z; Hjelm Jr, R P et al. (1986) Selective detection of rapid motions in spectrin by NMR. FEBS Lett 197:234-8
Lee, Y H; Currie, B L; Johnson, M E (1986) Interaction of a spin-labeled phenylalanine analogue with normal and sickle hemoglobins: detection of site-specific interactions through spin-label-induced 1H NMR relaxation. Biochemistry 25:5647-54